Prevalence of cancer-related cognitive impairment in pediatric patients and survivors of non-CNS cancers: A systematic review and meta-analysis

Background: Neurocognitive toxicity is a common sequela of cancer and its treatment, with 40-60% of childhood cancer survivors experiencing cancer-related cognitive impairment (CRCI) following cancer and its treatment. CNS cancers and CNS-directed therapy are considered to pose the greatest risk; however, such impairment has also been reported in non-CNS cancers, the most commonly diagnosed in children. Despite initial findings, no formal systematic assimilation of evidence has previously reported estimates in pediatric populations, or identified the influence of cancer, treatment, and patient variables. Thus, this review aims to investigate the prevalence of CRCI in pediatric non-CNS cancers. Methods: A systematic search was conducted using PubMed via MEDLINE, Scopus, PsycINFO via OvidSP, and CINAHL via EBSCOhost. Simple proportional meta-analyses were performed using PERSyst, and the certainty of evidence was assessed employing GRADE. Results: Twenty-six studies contributed to two cognitive domains - (1) global cognitive function and intelligence, and (2) achievement, aptitude and school readiness. Pooled prevalence estimates suggest that survivors of non-CNS cancers experience impairments in measures of intelligence (12.46%-18.05%) and attention (9.83%-12.05%). Non-pooled prevalence estimates ranged from 0-67% in global cognitive function and intelligence, and 0-73% in achievement, aptitude and school readiness. Conclusion: Survivors of non-CNS cancers experience significant impairments in these cognitive domains; however, certainty of evidence is generally low to very low, warranting cautious interpretation of prevalence estimates. Implication for Cancer Survivors: Understanding the prevalence of CRCI following childhood cancer can inform survivorship strategies and provide impetus for provision of dedicated supports, such as rehabilitation and school reintegration supports.